ASCO Daily News American Society of Clinical Oncology (ASCO)

Dr. John Sweetenham shares highlights from Day 3 of the 2024 ASCO Annual Meeting, including selected studies on the treatment of cancer cachexia, surgical approaches in advanced ovarian cancer, and advanced colorectal cancer with liver metastases.
TRANSCRIPT
Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my top takeaways on selected abstracts from Day 3 of the 2024 ASCO Annual Meeting. 
Today's selection features studies addressing the treatment of cancer cachexia and 2 studies of surgical approaches to the treatment of advanced ovarian cancer and of advanced colorectal cancer with liver metastases. 
My full disclosures are available in the transcript of this episode.  
Cachexia affects up to 80% of patients with advanced cancer and is thought to be directly responsible for 30% of cancer deaths, according to the National Cancer Institute. Despite these statistics, the condition remains understudied and there is no standard treatment. Current guidelines recommend dietary counseling and low-dose olanzapine or short courses of corticosteroids or progesterone analogues can be used to promote weight gain. However, the guidelines mainly point to evidence gaps. No drug therapy could be strongly endorsed to improve patient outcomes and no recommendations could be made regarding exercise. 
Dr. Tora Solheim from the Cancer Clinic at St. Olavs Hospital in Trondheim, Norway, today reported results from the MENAC trial in LBA12007, which tested an intervention that combined treatment with nonsteroidal anti-inflammatory medication ibuprofen, home-based exercise to improve endurance and muscle strength, nutritional counseling, and supplements containing omega-3 fatty acids, which, based on previous research, may enhance muscle mass in patients with cancer cachexia. This trial enrolled 212 patients with stage III or IV lung or pancreatic cancer from 17 sites in 5 countries. All patients were receiving palliative chemotherapy and either had cachexia or were at high risk of developing it. Half were randomly assigned to the intervention and half to standard care. For the exercise components of the intervention, patients were encouraged to engage in aerobic activity such as walking, swimming, or even household chores at least twice a week. They were also encouraged to perform strengthening exercises such as half squats, bicep curls, and knee lifts 3 times per week. 
Over 6 weeks, the trial found average body weight stabilized in the intervention group compared with a loss of 1 kg in the standard care group, but there were no differences between the two groups and the secondary endpoints of muscle mass and daily step count as measured by ActiGraph. Dr. Solheim pointed out that 6 to 8 weeks may be too early to observe any anabolic effects on muscle mass or function, but that this timeframe was chosen, she said, because previous studies, including her team’s own feasibility study had encountered high dropout rates among similar patient groups after 6 to 8 weeks. 
Although these are interesting data, I think they also pose many questions: Is maintaining 1 kg of body weight a meaningful endpoint? Did the patients report any improvement in other symptoms? How was at-home exercise monitored for compliance? Did we know whether the patients were fulfilling adequate amounts of exercise? And there are many more questions. I think the investigators should be congratulated for demonstrating the feasibility of conducting a randomized trial in this challenging patient group, and this will hopefully provide a basis for future studies exploring new interventions.
In LBA5505, Dr. Jean-Marc Classe presented data from the CARACO study, a randomized trial evaluating the use of retroperitoneal lymph node dissection in patients undergoing primary surgery or interval cytoreductive surgery after neoadjuvant chemotherapy for advanced epithelial ovarian cancer.  
To provide some context, an earl

Dr. John Sweetenham shares highlights from Day 2 of the 2024 ASCO Annual Meeting, including potentially practice-changing results in advanced Hodgkin lymphoma, intriguing data on the effect of metformin on active surveillance for prostate cancer, and the potential of AI to improve patient outreach and adherence to medical appointments.
TRANSCRIPT 

Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my top takeaways on selected abstracts from Day 2 of the 2024 ASCO Annual Meeting.  

Today's selection features potentially practice-changing results for patients with advanced stage Hodgkin lymphoma, results from a large trial testing the effects of metformin in patients on active surveillance for their prostate cancer, and early results giving insights into the benefits that artificial intelligence may bring to address disparities in cancer care.   

My full disclosures are available in the transcript of this episode.  

The first of today's abstracts is LBA7000, which reports the results from a large international randomized trial in patients with advanced Hodgkin lymphoma, presented by Dr. Peter Borchmann from the German Hodgkin Study Group. Since Hodgkin lymphoma typically affects adults in their 20s and 30s, the focus of clinical trials in recent years has been on achieving high rates of disease control while at the same time reducing the potential for short-term and long-term toxicities associated with classical chemotherapy and radiation therapy regimens. Particular emphasis has been given to reducing risk for secondary malignancy and impaired reproductive function in long-term survivors.  

Building on the back of previous studies from this group, the escalated BEACOPP regimen was modified to reduce the overall duration of treatment and the potential for toxicity by incorporating novel agents, including brentuximab vedotin. This novel regimen, known as BrECADD, was compared with escalated BEACOPP in a randomized trial, HD21. Patients received 4 or 6 cycles of therapy based on the response of their disease to the first 2 cycles assessed by interim PET scan. 1,482 patients were randomized, 740 to escalated BEACOPP and 742 to BrECADD, with median follow-up at 48 months. The 4-year progression-free survival was 94.3% with BrECADD, compared with 90.9% for escalated BEACOPP, with a hazard ratio of 0.66. These results are particularly noteworthy since 64% of patients on the BrECADD arm had a negative PET scan after 2 cycles of therapy and therefore received a total of just 4 cycles, reducing their risk of toxicity.   

On that note, lower rates of treatment related toxicity were observed with BrECADD. Specifically, hematologic toxicity and peripheral sensory neuropathy were less frequently seen. Female reproductive toxicity was lower with BrECADD, with more than 95% of women having normal FSH levels after 1 year on BrECADD, compared with 73% on escalated BEACOPP. Dr. Borchmann also noted that recovery of male reproductive function was improved with BrECADD, although details were not provided. These are impressive data, although no overall survival difference was observed. This is not surprising in view of the effective salvage therapies available to patients whose disease relapses after first-line therapy.  

The authors conclude that these results are unprecedented for the first-line treatment of Hodgkin lymphoma and that the BrECADD regimen should be considered as a new standard of care option. Although these results are likely to change practice in some parts of the world, particularly in Europe, it's less clear whether they will impact current treatments in the United States, where modifications to the ABVD regimen, including the addition of brentuximab vedotin and more recently nivolumab, have been the subject of recent randomized trials. That said, these data add to the increasing evidence that cure of advanced Hodgkin lymphoma is possible in m

In the first episode of a special daily series during the 2024 ASCO Annual Meeting, Dr. John Sweetenham shares highlights from Day 1, including exciting data on the CROWN trial in NSCLC, the ASC4First study in chronic myeloid leukemia, and the effects of high-deductible health plans on cancer survivorship.
TRANSCRIPT
Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. I'm delighted to bring you a special series of daily episodes from the 2024 ASCO Annual Meeting and to share my top takeaways on selected abstracts.  
Today, I'll be reviewing exciting new data in chronic myeloid leukemia, remarkable outcomes for patients with ALK-positive non-small cell lung cancer, and a compelling study on the effects of high deductible health plans on cancer survivorship.  
My disclosures are available in the transcript of this episode.  
LBA6500, the ASC4FIRST trial, is a phase 3 combination of asciminib with the current standard of care tyrosine kinase inhibitors, those being imatinib, nilotinib, dasatinib and bosutinib for the first line treatment of patients with chronic myeloid leukemia. The data from this large multinational study, conducted in 29 countries, were presented by Dr. Timothy Hughes from the Royal Adelaide Hospital in Australia. Some patients with chronic phase CML respond well to tyrosine kinase inhibitor therapy, and about one-third may eventually be able to stop therapy and will remain in remission, the so-called treatment free remission or TFR. Unfortunately, almost half of patients eventually need to change therapy due to resistance and intolerance, and most patients will need to remain on therapy for many years, possibly for life. 
Asciminib is the first BCR-ABL1 inhibitor to specifically target the ABL myristate pocket or STAMP and was designed to be highly potent but also highly specific, thus minimizing side effects and toxicity. In this large trial, which is the first randomized head-to-head comparison of asciminib with other tyrosine kinase inhibitors, 405 patients were randomized 1:1 to receive either asciminib at a dose of 80 milligrams daily or another investigator-selected TKI. The groups were well balanced for all patient characteristics, including ELTS risk. The primary objectives of the study were to compare the major molecular response rate at 48 weeks with an additional analysis for the patients who received imatinib as the investigator-selected TKI. With median follow-up at 16.3 months for patients receiving asciminib and 15.7 months for those receiving the other TKIs, the 48-week MMR rates were 68% for asciminib compared with 49% for the other investigators-selected TKIs. 
The rates of MR4 after 48 weeks, a deep molecular response which is a prerequisite to be considered for treatment free remission, were 39% for asciminib compared to 21% for the investigator-selected TKI. Tolerability and safety were excellent for asciminib, with only 5% discontinued due to toxicity compared to 10% for the other TKI arm. Frequently observed toxicities with asciminib included thrombocytopenia and neutropenia. The investigators concluded that asciminib is the only agent to show a statistically significant improvement in efficacy and toxicity in this patient group when compared with all other TKIs, and that asciminib has the potential to become the preferred standard of care for the first line treatment of CML. Follow-up on the study continues, but there is no question that these are exciting and probably practice-changing results. 
The next exciting study, LBA8503, was presented by Dr. Benjamin Solomon from the Peter MacCallum Cancer Centre in Melbourne, Australia. This presentation was an update of the CROWN study for patients with previously untreated advanced ALK-positive non-small cell lung cancer. Lorlatinib is a third-generation brain-penetrating ALK inhibitor which was compared with crizotinib in the CROWN-3 study. This phase 3 study enrolled 296 patient

Dr. Shaalan Beg and Dr.Mohamed Salem discuss key abstracts that will be presented at the 2024 ASCO Annual Meeting, including hypoxia-response CAR T- cell therapy for solid tumors, GPC3-specific CAR T- cell therapy in hepatocellular carcinoma, and the promising efficacy of targeted therapies in GI cancers. 
TRANSCRIPT
Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center. In today's episode, we'll be discussing some key abstracts in GI cancers that will be presented at the 2024 ASCO Annual Meeting. I'm delighted to welcome Dr. Mohammed Salem, a GI medical oncologist at the Levine Cancer Institute at Atrium Health, for this discussion.
Our full disclosures are available in the transcript of this episode.
Mohammed, it's great to have you back on the podcast.
Dr. Mohamed Salem: Thank you, Dr. Beg. It's always a pleasure to be here. Thanks for having me. 
Dr. Shaalan Beg: So we're seeing more and more exciting data emerge on the role of ctDNA in GI cancers. And that's a topic that we've covered fairly extensively on the podcast. This year, in Abstract 3513, investigators used a novel, highly sensitive HPV ctDNA assay to evaluate the clinical outcomes of HPV ctDNA status in people with localized anal cancer treated with chemoradiation. And we know that prior HPV infection is associated with 90% of a**l cancers. Can you give us a summary of the study and why it's so important to the clinical care we're giving our patients today? 
Dr. Mohamed Salem: Sure. So, as you already alluded to, in the current era of precision oncology or precision medicine in general, there is an effort to try to maximize treatment efficacy and minimize the side effects. We're trying to understand how to do that by developing more biomarkers. I think this was a very interesting study that was led by Dr. Morris of MD Anderson. As you mentioned, he tried to determine the correlation between that circulating tumor DNA at different timelines and also associated that with the relapse. Obviously, as we all know, HPV infection is linked to about over 90% of anal cancers, and a**l cancer is increasingly common in the U.S. 
The study design includes patients from stage 1, 2, and 3 a**l cancer treated with curative intent concurrent chemo radiation and the plot sample to collect circulating DNA was taken at five weeks of treatment and then at various intervals, including 3months, 6  months, 9 months and 12 months, to detect the HPV circulating DNA. And the analysis was done to correlate detection of circulating DNA with a relapse. 
So what they observed is after collecting the samples at the end of the treatment, which is 5 weeks, followed by 3 months, 6 months, 9 months, and 12 months following treatment using the correlation between the detection of circulating tumor DNA as well as the recurrence rate, they were able to identify that about 22% was seen at 5 weeks, 13% was seen at three months, then 10% was seen at 6 months, and 0% actually was seen at 12 months.
In the final analysis, they concluded that detection of circulating DNA at 3 months was significantly associated with a relapse rate of those patients. And also, they looked at the baseline stage, T stage, end stage, age and other perhaps prognostic factors. But the clinical implication of that trial is this finding supports the potential of integrating now the circulating DNA analysis and routine post-treatment surveillance, which hopefully will help us identify those patients with high risk of relapse and whether they can be treated with adjuvant therapy  in context-free drug trial or even like more close surveillance. Obviously, this is a very novel study, so it needs validation. Also, we need to understand more about the platform used because with the immersion technology and how fast this field is moving, I think

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss promising combination therapies and other compelling advances in genitourinary cancers in advance of the 2024 ASCO Annual Meeting.
TRANSCRIPT
Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of genitourinary cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that will be featured at the 2024 ASCO Annual Meeting. 
Our full disclosures are available in the transcript of this episode.
Jeanny, it’s great to have you on the podcast.
Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal. It's a pleasure to be here.
Dr. Neeraj Agarwal: So, Jeanny, let's start with some bladder cancer abstracts. Could you tell us about the Abstract 4509 titled, “Characterization of Complete Responders to Nivolumab plus Gemcitabine Cisplatin versus Gemcitabine Cisplatin Alone in Patients with Lymph Node Only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial.” 
Dr. Jeanny Aragon-Ching: Of course, Neeraj, I would be delighted to. First, I would like to remind our listeners that the CheckMate 901 trial was a randomized, open-label, phase 3 study, in which this particular sub-study looked at cisplatin-eligible patients with previously untreated, unresectable, or metastatic urothelial carcinoma who were assigned to receive the combination of gemcitabine and cisplatin, followed by up to 2 years of nivolumab or placebo. Based on the data presented at ESMO 2023 and subsequently published in the New England Journal of Medicine, which shows significantly improved progression-free survival and overall survival in patients receiving the combination of gemcitabine, cisplatin, and nivolumab, this regimen was approved in March 2024 as a first-line therapy for patients with unresectable or metastatic urothelial carcinoma. 
In the abstract that will be featured at ASCO this year, Dr. Matt Galsky and colleagues present a post-hoc analysis that aims to characterize a subset of patients with complete response as well as those with lymph node-only metastatic disease. In patients receiving the experimental treatment, 21.7% achieved a complete response, while 11.8% of the patients in the control arm achieved a complete response.  Among these complete responders, around 52% had lymph- node-only disease in both arms. Furthermore, when characterizing the subgroup of patients with lymph-node-only disease, those receiving the combination of gemcitabine-cisplatin plus nivolumab had a 62% reduction in the risk of progression or death and a 42% reduction in the risk of death compared to those treated with gemcitabine-cisplatin alone.  The median overall survival in the experimental arm in this subgroup was around 46.3 months, while it was only 24.9 months in the control arm. The ORR in patients with lymph-node-only disease receiving gem-cis plus nivo was about 81.5% compared to 64.3% in those treated with gem-cis alone.
Dr. Neeraj Agarwal: Thank you, Jeanny, for the excellent summary of this abstract. We can say that nivolumab plus gemcitabine-cisplatin induced durable disease control and clinically meaningful improvements in OS and PFS compared to gem-cis alone in patients with lymph- node-only metastasis, and deserves to be considered as one of the options for these patients. 
In a similar first-line metastatic urothelial carcinoma setting, Abstract 4502, also reported data on a recently approved combination of enfortumab vedotin and pembrolizumab. Can you tell us more about this abstract, Jeanny?
Dr. Jeanny Aragon-Ching:

Dr. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond. 
TRANSCRIPT
Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center. 
You will find our full disclosures in the transcript of this episode. 
Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work. 
Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO. 
Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time? 
Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo. 
The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we wou